MSPI RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM AT THE GLYCOPROTEIN HORMONE ALPHA-SUBUNIT LOCUS - ASSOCIATION OF CERTAIN GENOTYPES WITH NEOPLASIA

A restriction fragment length polymorphism (RFLP) in the human glycopr otein hormone common a-subunit gene has been identified and partially characterized in normal lymphocytes and placentae, established tumor c ell lines, and tumor biopsy samples. High molecular weight DNA was dig ested with the restriction endonuclease MspI, separated by electrophor esis in agarose gels, transferred to nylon membranes by the method of Southern, and hybridized to P-32-labeled human chorionic gonadotropin alpha-subunit cDNA. After autoradiography, bands were detected at 5.3, 3.3, 2.1, 1.6, 0.8 and 0.6 kbp. Presence of the 5.3, 3.3 and 0.6 kbp bands was invariant and uninformative. Patterns missing the 0.8 kbp ba nd and both the 2.1 and 1.6 kbp bands are consistent with separate all eles that occur in placental and lymphocyte DNA with frequencies of 0. 44 (15/34) and 0.06 (2/34), respectively. Presence of all three bands (2.1, 1.6 and 0.8 kbp) is indicative of heterozygosity, occurring at a frequency of 0.50 (17/34). Additional restriction patterns, not yet o bserved in DNA isolated from term placentae or circulating lymphocytes , were detected in DNA obtained from tumor cell lines and fresh tumor tissues at frequencies of 0.79 (15/19) and 0.59 (10/17), respectively. Thus, particular a-subunit genotypes are disproportionately represent ed in tumor-derived DNA, occurring at frequencies 10- to 13-times high er than would be predicted from their occurrence in normal tissue. Pai red normal and tumor tissues from the same individual exhibited identi cal hybridization patterns, suggesting that this RFLP may be represent ative of a predisposition toward a variety of neoplasias rather than i ndicative of a change in DNA structure at or near this locus as a resu lt of tumor development. (C) 1997 Elsevier Science B.V.